Show simple item record

dc.creatorAranđelović, Jovana
dc.creatorSantrač, Anja
dc.creatorBatinić, Bojan
dc.creatorTodorović, Lidija
dc.creatorStevanović, Vladimir
dc.creatorTiruveedhula, Veera Venkata Naga Phani Babu
dc.creatorSharmin, Dishary
dc.creatorRashid, Farjana
dc.creatorStanojević, Boban
dc.creatorCook, James
dc.creatorSavić, Miroslav
dc.date.accessioned2022-07-27T12:31:30Z
dc.date.available2022-07-27T12:31:30Z
dc.date.issued2022
dc.identifier.issn1755-5930
dc.identifier.urihttps://farfar.pharmacy.bg.ac.rs/handle/123456789/4203
dc.description.abstractAims: GABAergic modulation involved in cognitive processing appears to be substan- tially changed in Alzheimer's disease (AD). In a widely used 5xFAD model of AD, we aimed to assess if negative and positive allosteric modulators of α5 GABA A receptors (NAM and PAM, respectively) would affect social interaction, social, object and spatial memory, and neuroinflammation. Methods: After 10-day treatment with PAM, NAM, or solvent, 6-month-old trans- genic and non-transgenic 5xFAD mice underwent testing in a behavioral battery. Gene expressions of IL-1β, IL-6, TNF-α, GFAP, and IBA-1 were determined in hippocampus and prefrontal cortex by qPCR. Results: PAM treatment impaired spatial learning in transgenic females compared to solvent-treated transgenic females, and social recognition in transgenic and non- transgenic males. NAM treatment declined social interaction in transgenic and non- transgenic males, while had beneficial effect on cognitive flexibility in non-transgenic males compared to solvent-treated non-transgenic males. Transgenic animals have not fully displayed cognitive symptoms, but neuroinflammation was confirmed. NAM reduced proinflammatory gene expressions in transgenic females and astrogliosis in transgenic males compared to pathological controls. Conclusion: PAM and NAM failed to exert favorable behavioral effects in transgenic animals. Suppression of neuroinflammation obtained with NAM calls for more studies with GABAergic ligands in amyloid beta- and/or tau-dependent models with promi- nent neuroinflammation.
dc.publisherJohn Wiley and Sons Inc
dc.relationinfo:eu-repo/grantAgreement/MESTD/inst-2020/200161/RS//
dc.relationNIH for generous financial support (DA- 043204, R01NS076517)
dc.relationMilwaukee Institute for Drug Discovery and the University of Wisconsin-Milwaukee's Shimadzu Laboratory
dc.relationNational Science Foundation, Division of Chemistry [CHE-1625735]
dc.rightsopenAccess
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceCNS Neuroscience & Therapeutics
dc.titleEffects of α5 GABAA receptor modulation on social interaction, memory, and neuroinflammation in a mouse model of Alzheimer's disease
dc.typearticle
dc.rights.licenseBY
dc.citation.volume28
dc.citation.issue11
dc.citation.spage1767
dc.citation.epage1778
dc.citation.rankM21
dc.identifier.wos000823616200001
dc.identifier.doi10.1111/cns.13914
dc.identifier.scopus2-s2.0-85134060517
dc.identifier.fulltexthttp://farfar.pharmacy.bg.ac.rs/bitstream/id/9974/bitstream_9974.pdf
dc.type.versionpublishedVersion


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record